Bacterial Template Synthesis of Multifunctional Nanospindles for Glutathione Detection and Enhanced Cancer-Specific Chemo-Chemodynamic Therapy

Biological synthetic methods of nanoparticles have shown great advantages, such as environmental friendliness, low cost, mild reaction conditions, and enhanced biocompatibility and stability of products. Bacteria, as one of the most important living organisms, have been utilized as bioreducing nanofactories to biosynthesize many metal nanoparticles or compounds. Here, inspired by the disinfection process of KMnO4, we for the first time introduce bacteria as both the template and the reducing agent to construct a novel tumor microenvironment-responsive MnOx-based nanoplatform for biomedical applications in various aspects. It is found that the bacterium/MnOx-based nanospindles (EM NSs) can efficiently encapsulate the chemotherapeutic agent doxorubicin (DOX), leading to the fluorescence quenching of the drug. The as-formed DOX-loaded EM NSs (EMD NSs) are proven to be decomposed by glutathione (GSH) and can simultaneously release DOX and Mn2+ ions. The former can be utilized for sensitive fluorescence-based GSH sensing with a limit of detection as low as 0.28 mu M and selective cancer therapy, while the latter plays important roles in GSH-activated magnetic resonance imaging and chemodynamic therapy. We also demonstrate that these nanospindles can generate oxygen in the presence of endogenous hydrogen peroxide to inhibit P-glycoprotein expression under hypoxia and can achieve excellent tumor eradication and tumor metastasis inhibition performance. Taken together, this work designs a multifunctional bacterially synthesized nanomissile for imaging-guided tumor-specific chemo-chemodynamic combination therapy and will have implications for the design of microorganism-derived smart nanomedicines.